This invention relates to novel nitrosourea derivatives which exhibit a high level of activity against the leukemia and tumors with a low toxicity and a good stability against humidity and which are therefore useful in the therapeutic treatments of the leukemia and tumors. This invention further relates to a process for the preparation of such novel nitrosourea derivatives and to their use for pharmaceutical purposes.
There are a variety of compounds which have been proposed as being effective for inhibiting the leukemia and tumors and one class of which is nitrosourea derivatives. Among the nitrosourea derivatives, there may be mentioned Streptozotocin [N-(N'-methyl-N'-nitroso-carbamoyl)-D-glucosamine] and their derivatives such as methyl glucosaminides as most typical examples, but they are not satisfactory yet because of insufficient activity against the leukemia and tumors and/or undesirable side effect thereof. Another class of the nitrosourea derivatives is glycosyl derivatives of nitrosoureas which I have most recently proposed, of which the most preferred example is 1-(2-chloroethyl)-3-(.beta.-D-glucopyranosyl)-1-nitrosourea which was found to have a remarkably high inhibitory activity against a variety of leukemia and tumors with a low toxicity and a low side effect, but to be somewhat hygroscopic.
I have now found that certain novel nitrosourea derivatives, as hereinafter defined, exhibit a high inhibitory activity against the leukemia and tumors with a low toxicity as evidenced by in vivo tests and has a good stability against humidity.
According to one aspect of this invention, therefore, there are provided as novel compounds nitrosourea derivatives of the formula: ##STR2## wherein R.sup.1 represents a hydroxyl or an alkanoyloxy containing 2-4 carbon atoms; R.sup.2 represents a hydrogen or an alkanoyl containing 2-4 carbon atoms; R.sup.3 represents an alkanoyl containing 2-4 carbon atoms; and R.sup.4 represents an alkyl containing 1-4 carbon atoms or a halo-substituted alkyl containing 1-4 carbon atoms.